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AbstractBackgroundImmune checkpoint inhibitor (ICI) therapy has led to significant improvement in outcomes for patients with nononcogene‐driven advanced non–small cell lung cancer (NSCLC). The rate of crossover and receipt of postprotocol ICI in frontline trials for advanced NSCLC has not been systematically evaluated.MethodsClinicalTrials.gov was used to identify phase 3 studies evaluating the use of immunotherapy or combination chemoimmunotherapy against chemotherapy alone in the frontline management of advanced NSCLC. Data on outcomes, rate of crossover and/or subsequent post‐protocol receipt of immunotherapy, and the start dates of these clinical trials were then extracted.ResultsTwenty‐three frontline trials in nononcogene‐driven advanced NSCLC were identified. Six trials with ICI monotherapy/dual ICI therapy and 17 trials evaluating chemotherapy/ICI in first‐line advanced NSCLC were included in the analysis. The crossover rate ranged 0% to 54% in ICI monotherapy/dual ICI trials and 0% to 52% in chemotherapy/ICI trials. Nineteen of 23 trials provided information on subsequent postprotocol therapies. Among the trials not allowing crossover, postprotocol ICI was administered to 17% to 45.8% of patients. Information regarding the eventual receipt of ICI therapy was available for 22 of 23 trials. Of 6631 patients, 2507 (37.8%) randomized to the control arm eventually received ICI therapy.ConclusionThe rate of crossover and postprotocol ICI use was low in frontline trials for first‐line NSCLC incorporating ICI. Given the proven improved overall survival of ICI in a broad population, there is a need to ensure availability of this life‐prolonging therapy in future trials, either by crossover treatment or postprotocol administration.

Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease’s recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]

The treatment of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) has evolved to include several new options. The NCCN Guidelines for WM/LPL provide a framework on which to base decisions regarding diagnosis, treatment, assessment of response to treatment, and follow-up of both newly diagnosed and previously treated WM/LPL.

Introduction: The performance of automated left ventricular ejection fraction (LVEF) assessment in patients with altered cardiac chamber geometry, such as those with obstructive hypertrophic cardiomyopathy (HCM), is not well described. Aims: Accurate assessment of LVEF is required for dose titration and continuation of myosin inhibitors in obstructive HCM. From the VALOR-HCM trial (NCT04349072), the agreement of two commercially available software packages was compared with blinded core lab assessment of LVEF. Methods: From baseline and week 16, among 112 patients randomized to either mavacamten or placebo, 178 echocardiograms were analyzed. Representative clips were manually selected, and automated LVEFs were calculated. Comparisons of LVEFs were made using Pearson’s correlation coefficients and Bland-Altman analysis. Results: With core lab assessment, the overall median LVEF was 68% (Q1 66%, Q3 70%). The correlation with vendor 1 was moderate (r = 0.47, 95% CI 0.35-0.58, p <0.001) and weak with vendor 2 (r =0.21, 95% CI 0.07-0.35, p =0.004). Correlation was also weak between vendor 1 and 2 (r = 0.14, 95% CI 0.00-0.28, p = 0.06). Vendors 1 and 2 had an underestimation bias of LVEF of 8% (95% CI 6-9%) and 8% (95% CI 7-9%), respectively, compared to core lab LVEF (Figure 1). Conclusions: In VALOR-HCM, the concordance of LVEF between different commercially available software packages with each other and with a core lab assessment was limited. Further study is needed to evaluate and improve the performance of automated LVEF tools in obstructive HCM patients who have altered cardiac chamber geometry.

Introduction: Sepsis and its associated systemic inflammatory response syndrome in the heart can lead to septic cardiomyopathy. We aim to explore new onset cardiac dysfunction in septic shock patients and its association of right heart dysfunction with hospital outcomes. Hypothesis: Early development of correct ventricular abnormalities due to septic shock may lead to worse hospital outcomes. Methods: We conducted a retrospective study of 102 patients who were hospitalized at the Mayo Clinic between August 2018 and September 2022 with septic shock and had at least one pre-sepsis echo (within one year before admission) and one post-sepsis echo (within seven days of access). Information on patient demographics, comorbidities, echo parameters, and outcomes was collected from our sepsis database and retrospective chart review. Categorical variables were described as percentages and compared by Chi-square test, and continuous variables as medians and compared using an independent sample t-test. Statistical analysis was performed using BlueSky Statistics v10.3.1. Results: Our study included 102 patients with a median age of 68 (55, 78) years, the majority being men (68%) and Caucasians (80%). Between pre- and post-sepsis echos, there was a noticeable decrease in LVEF (60% vs 50.5 %; p=0.002). Moreover, there was an increase in reduced RV function (31.6% vs. 62.6%, p<0.001), reduced LV function (56.5% vs. 85.2%, p=0.048), and RV dilatation (35.8% vs. 51.5%, p=0.03). There was also a noticeable decrease in IVC collapsibility of more than 50% (65.9% vs 22.9%, p<0.001). There was no significance in terms of demographics, comorbidities, and baseline vitals and labs among patients with RV dysfunction and without RV dysfunction except for a lower LVEF (49% vs 62 %, p= 0.004) and decreased >50 % IVC collapsibility (14.5% vs 48%, p=0.005) in RV dysfunction group. We found no differences in hospital mortality, ICU and hospital LOS, or mechanical ventilation requirements amongst patients with RV abnormalities in function and size. Conclusions: Our retrospective study shows that abnormalities in RV function and RV size are commonly observed in the initial week of septic shock. However, such RV abnormalities did not translate into worse hospital outcomes.

Background: Up to 70% of patients with cardiogenic shock (CS) will survive hospitalization, yet studies on the outcomes of CS survivors are scarce. Hypothesis: We hypothesized that CS survivors would be at high risk of rehospitalization, particularly CS without acute myocardial infarction (AMI) who may have chronic heart failure (HF). Methods: We used the Nationwide Readmissions Database (NRD) to examine adult patients who were discharged alive after an index CS admission from 2016-2019. We compared demographic and clinical features during the index admission and the readmission mortality rate between the AMI-CS versus non-AMI-CS groups. We analyzed the cumulative hazard for all-cause readmission within 90 days after index hospitalization using Kaplan-Meier curves. Results: We included 134,793 survivors of CS hospitalization from 2016 to 2019 who were discharged to home or a long-term facility, including 43.9% with AMI-CS and 56.1% with non-AMI-CS. The demographics and clinical features differed between the AMI-CS and non-AMI-CS groups, with more HF and non-cardiac comorbidities in the non-AMI-CS group. The non-AMI-CS patients were more likely to be readmitted after discharge, with a higher 90-day readmission rate compared to the AMI-CS group (31.6% vs 25.9%, p <0.001; Figure). During the readmission, the non-AMI-CS group had a higher rate of repeat CS presentation compared to the AMI-CS group (8.9% vs.. 6.1%, p < 0.001). In-hospital mortality during readmission was higher in the non-AMI-CS group (8.6% vs.7.2%, p < 0.001). Conclusions: Nearly one-third of CS survivors require readmission within 90 days after their index hospitalization. Non-AMI-CS patients have a higher re-admission rate after their index hospitalization and worse outcomes during readmission. This analysis identifies an unmet need and an important opportunity to improve long-term outcomes for CS survivors.

The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These include new combinations with second generation proteasome inhibitors (PI); second generation immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others. Most patients with MM undergo several cycles of remissions and relapse, and therefore need multiple lines of combination therapies. Selecting treatment options for relapsed/refractory MM requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered. The NCCN Guidelines for MM provide a framework on which to base decisions regarding workup, treatment, and follow-up of newly diagnosed and previously treated MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to relapsed/refractory disease.